Study of lactonization process in deoxycholic acid analogs by modeling: structure of 3α-acetoxy-24-nor-5β-cholano-12α,24-lactone

Abstract

Abstract The title compound was synthesized from 3α-acetoxy-12α-hydroxy-24-nor-5β-cholan-23-oic acid by treating it with dichloroethylphosphate and triethylamine. The crystals are orthorhombic, space group P212121, a = 19.166(2) Å, b = 14.109(2) Å, c = 8.246(1) Å, V = 2229.9(6) Å3, Z = 4, D c = 1.189 g cm−3, λ(CuKα ) = 1.5418 Å, μ = 0.55 mm−1, F(000) = 880, T = 298 K. The structure was solved by direct methods and refined to R = 0.049 for 894 observed reflections collected on a CAD-4 diffractometer. The molecules in the crystal are in their monolactone form. Energy calculations, based on molecular modeling were carried out for similar molecules containing 6- to 11-membered monolactone and 12- to 22-membered bislactone rings. The relative minimum energy values, obtained by MMX calculations, show a considerable decrease for monolactone rings with less than eight members, and a considerable increase for the bislactones with less than sixteen atoms. The MMX calculations are in agreement with current experimental results which indicate that the monolactonization occurs only in cases where the number of atoms forming the lactone ring is less than eight.